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ZIP2 and ZIP4 Mediate Age-Related Zinc Fluxes Across the Retinal Pigment Epithelium

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Abstract

Decreases in systemic and cellular levels of zinc (Zn2+) during normal aging correlate with several age-related pathologies including age-related macular degeneration. Zn2+ homeostasis in tissues is not only dependent on dietary intake but also on optimal expression and function of its influx (ZIP) and efflux (ZnT) transporters. We recently showed that many of the Zn2+ transporters are expressed by the retinal pigment epithelial (RPE) cells. In this study, we present evidence that RPE cells contain less endogenous Zn2+ with increased aging and transport this ion vectorially with greater transport from the basal to apical direction. Expression of two Zn2+ influx transporters, ZIP2 and ZIP4, is reduced as a function of RPE age. Gene silencing of ZIP2 and ZIP4 in RPE cells from young donors or their overexpression in cells from older donors confirms that these two transporters are essential in controlling Zn2+ influx and sequestration in RPE cells. Both transporters are distributed on the basal surface of the RPE where they are likely to control Zn2+ homeostasis in the outer retina.

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Abbreviations

ZIP2:

Zinc influx transporter 2

ZIP4:

Zinc influx transporter 4

Zn2+ :

Zinc ion

RPE:

Retinal pigment epithelium

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Acknowledgments

This work was supported by grants from the Ben Franklin Foundation, PA, USA and NEI Core Grant P30 EY01931 and by an unrestricted grant from Research to Prevent Blindness, Inc. to the Medical College of Wisconsin (PI: Dr. Janice M Burke)

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Authors and Affiliations

  1. Department of Neural and Behavioral Sciences, College of Medicine, Pennsylvania State University, Hershey, PA, USA

    Kar Wah Leung, Anzor Gvritishvili, Yanling Liu & Joyce Tombran-Tink

  2. Department of Ophthalmology, College of Medicine, Pennsylvania State University, 500 University Drive Hershey, Hershey, PA, 17033, USA

    Joyce Tombran-Tink

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  1. Kar Wah Leung
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Correspondence to Joyce Tombran-Tink.

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Leung, K.W., Gvritishvili, A., Liu, Y. et al. ZIP2 and ZIP4 Mediate Age-Related Zinc Fluxes Across the Retinal Pigment Epithelium. J Mol Neurosci 46, 122–137 (2012). https://doi.org/10.1007/s12031-011-9536-0

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